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Updated: Aug 1, 2026
Transverse Aortic Constriction in Mice
Published on: April 22, 2010
Cardiac fibrosis in mice lacking brain natriuretic peptide
1Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
Insights
Brain natriuretic peptide (BNP) acts as an antifibrotic factor in the heart. BNP deficiency in mice leads to increased cardiac fibrosis, particularly under pressure overload, highlighting its role in regulating ventricular remodeling.
Area of Science:
- Cardiology
- Molecular Biology
- Physiology
Background:
- Cardiac fibrosis, characterized by fibroblast proliferation and extracellular matrix deposition, contributes to myocardial stiffness and ventricular dysfunction in cardiovascular diseases.
- Brain natriuretic peptide (BNP) is elevated in heart failure, but its specific function in cardiac remodeling remains unclear.
Purpose of the Study:
- To investigate the role of Brain natriuretic peptide (BNP) in cardiac fibrosis and ventricular remodeling.
- To determine if BNP acts as an endogenous antifibrotic factor in the heart.
Main Methods:
- Generation of mice with targeted disruption of the BNP gene (Nppb(-/-) mice).
- Assessment of cardiac fibrosis in Nppb(-/-) mice under basal conditions and in response to ventricular pressure overload.
- Comparison with wild-type littermates (Nppb(+/+) mice).
Main Results:
- Nppb(-/-) mice exhibited multifocal fibrotic lesions in the ventricles without systemic hypertension or hypertrophy.
- Ventricular pressure overload exacerbated cardiac fibrosis in Nppb(-/-) mice, with increased lesion size and number.
- Wild-type littermates did not show similar focal fibrotic changes under pressure overload.
Conclusions:
- Brain natriuretic peptide (BNP) functions as a cardiomyocyte-derived antifibrotic factor in vivo.
- BNP plays a crucial role as a local regulator of ventricular remodeling, particularly in response to stress.
Abstract:
Cardiac fibrosis, defined as a proliferation of interstitial fibroblasts and biosynthesis of extracellular matrix components in the ventricles of the heart, is a consequence of remodeling processes initiated by pathologic events associated with a variety of cardiovascular disorders, which leads to abnormal myocardial stiffness and, ultimately, ventricular dysfunction. Brain natriuretic peptide (BNP) is a cardiac hormone produced primarily by ventricular myocytes, and its plasma concentrations are markedly elevated in patients with congestive heart failure and acute myocardial infarction. However, its precise functional significance has been undefined. In this paper, we report the generation of mice with targeted disruption of BNP (Nppb(-/-) mice). We observed multifocal fibrotic lesions in the ventricles from Nppb(-/-) mice. No signs of systemic hypertension and ventricular hypertrophy are noted in Nppb(-/-) mice. In response to ventricular pressure overload, focal fibrotic lesions are increased in size and number in Nppb(-/-) mice, whereas no focal fibrotic changes are found in wild-type littermates (Nppb(+/+) mice). This study establishes BNP as a cardiomyocyte-derived antifibrotic factor in vivo and provides evidence for its role as a local regulator of ventricular remodeling.
